How to kill derek simmons?

During the first fight with him, it's important to stay as far away from him as possible (Simmons will knock you off the train otherwise), but still be close enough that your shots don't miss due to the train's movements. As you weaken him, he'll occasionally revert to human form; if you need space, you can run around him during this time.

If you shoot him enough times while he's in human form, he'll drop to his knee and you'll be given a button-mash cue where Leon or Helena can start smacking Simmons around. In 2 player mode, you can surround Simmons and shoot him from the back and front simultaneously.

Eventually, he'll throw Leon onto another train and chase him, forcing Leon to run away while Helena covers him. Once Leon reaches Helena again, Simmons will run alongside the train they're in and fire a gattling gun-like appendage at them. Just keep shooting him. He'll eventually force Leon and Helena onto the train's roof, then he'll charge the train they're on head-on. Just shoot him to end the first fight.

For the second round, he turns into a dinosaur-like B.O.W. There will be explosive barrels around the area. Lure him next to them and shoot them to almost always instantly force him back into human form. Then just shoot and beat him until he turns back; repeat this until you're forced to shoot at him from a turret. Aim for his eye and you'll evetually be thrown off the turret, then you can go back to repeating the above process until he's beaten.

At one point, he'll rip open a fuel tank; the fuel can be shot, causing it to ignite and force Simmons back into human form if he's stepping in it. You can also forgo shooting the tanks and just shoot him. There's a weak spot on his underside (a group of eyes in some sort of hole) and on his back (you need to destroy the plating protecting it). Ada will have an easier time destroying the plating and shooting the weak spot from her helicopter.

Round 3 is the same as Round 1. Keep away from him and shoot. You'll have more room now and can easily dodge his charges. However, he will now shoot at you, can impale you if you're within the reach of his gattling appendage, and can revert to human form and quickly hit you with a grab combo.

Round 4, he's in human form and stuck in one place, but he can stab you if you get too close. Just shoot him.

Round 5, he turns into a giant fly. Aim at his eyes to keep him from killing Leon before he regroups with Helena. Once you regroup, the real battle starts. You'll see a zombie impaled by an antenna; you'll want to kill all the other zombies nearby before focusing on Simmons. Once that's done, shoot at the glowing joints that connect Simmons's legs to his stomach. Try to destroy as many as possible, but just one is fine.

He'll try to absorb a zombie to heal his leg, and will grab the zombie impaled by the antenna. The antenna will be stuck in his leg and lightning will strike him, destroying the leg again and dealing massive damage.

Quickly grab the antenna and impale a zombie with it. If you're quick enough and manage to clear out any excess zombies (or ones who are too close) Simmons will grab the zombie and antenna and attempt to heal himself again only to meet with the same fate. Repeat this one more time and he'll crumple to the ground; impale a zombie with the antenna, remove the excess zombies, and then shoot his eyes. If done right, he'll grab the zombie and antenna, then lighting will strike his head.

Round 6, pick up the rocket launcher, point it at Simmons, then shoot and watch as he falls to his inevitable death.